NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China

AIM: To investigate the association of the NQO1 (C609T) polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in North China. METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 317 cancer patients (193 ESCC and 124 GCA) and 165 unrelated healthy controls. RESULTS: The NQO1 C609T C/C, C/T and T/T genotype frequency among healthy controls was 31.5 %, 52.1 % and 16.4 % respectively. The NQO1 T/T genotype frequency among ESCC patients (25.9 %) was significantly higher than that among healthy controls (chi(2)=4.79, P=0.028). The NQO1 T/T genotype significantly increased the risk for developing ESCC compared with the combination of C/C and C/T genotypes, with an age, sex and smoking status adjusted odds ratio (OR) of 1.78 (1.04-2.98). This increased susceptibility was pronounced in ESCC patients with family histories of upper gastrointestinal cancers (UGIC) (adjusted OR=2.20, 95 % CI=1.18-3.98). Similarly, the susceptibility of the NQO1 T/T genotype to GCA development was also observed among patients with family histories of UGIC, with an adjusted odds ratio of 2.55 (95 % CI=1.21-5.23), whereas no difference in NQO1 genotype distribution was shown among patients without family histories of UGIC. CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate the individuals at high risk for developing ESCC and GCA in North China.     

NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China

AIM: To investigate the association of the NQO1 (C609T)polymorphism with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in North China.METHODS: The NQO1 C609T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 317 cancer patients (193 ESCC and 124 GCA) and 165 unrelated healthy controls.RESULTS: The NQO1 C609T C/C, c/r and T/T genotype frequency among healthy controls was 31.5 %, 52.1% and 16.4 % respectively. The NQO1 T/T genotype frequency among ESCC patients (25.9 %) was significantly higher than that among healthy controls (X2=4.79, P=0.028). The NQO1T/T genotype significantly increased the risk for developing ESCC compared with the combination of C/C and C/T genotypes,with an age, sex and smoking status adjusted odds ratio (OR)of 1.78 (1.04-2.98). This increased susceptibility was pronounced in ESCC patients with family histories of upper gastrointestinal cancers (UGIC) (adjusted OR=2.20, 95 %CI=1.18-3.98). Similarly, the susceptibility of the NQO1 T/T genotype to GCA development was also observed among patients with family histories of UGIC, with an adjusted odds ratio of 2.55 (95 % CI=1.21-5.23), whereas no difference in NQO1 genotype distribution was shown among patients without family histories of UGIC.CONCLUSION: Determination of the NQO1 C609T genotype may be used as a stratification marker to predicate the individuals at high risk for developing ESCC and GCA in North China.     

Interleukin-10 -1082 promoter polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high-incidence region of north China

AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China. METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203 ESCC and 152 GCA) and 443 healthy controls. RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42 and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively). Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10, 95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%, 39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6% and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P>0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95% CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46) in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes. CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.     

Polymorphisms in promoter region of FAS and FASL gene and risk of gastric cardiac adenocarcinoma

Background and Aim: The FAS and FASL system play an important role in regulating apoptotic cell death. This study was designed to investigate the correlation of FAS‐1377 G/A, ‐670 A/G and FASL‐844 T/C polymorphisms with susceptibility to gastric cardiac adenocarcinoma in a population of a high‐incidence region of Hebei Province. Methods: FAS‐1377 G/A, ‐670 A/G and FASL‐844 T/C polymorphisms were genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis in 262 gastric cardiac carcinoma (GCA) patients and 524 healthy controls. Results: Family history of upper gastrointestinal cancer (UGIC) might increase the risk of developing GCA (age‐ and sex‐adjusted odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.02–1.86). The overall allelotype and genotype distributions of FAS‐1377 G/A, and FASL‐844 T/C polymorphisms in GCA patients did not significantly differ from that in healthy controls (P > 0.05). Compared with individuals with a FAS‐670 A/A genotype, individuals with an A/G genotype in a smoker group had a lower risk of developing GCA (age, sex, and family history of UGIC adjusted OR = 0.55, 95% CI = 0.34–0.88). When the genotypes of FAS and FASL single nucleotide polymorphisms (SNP) were combined to analyze, no significant correlation was found between these SNP and the risk for GCA development. Conclusion: In the high‐incidence region of Hebei Province, FAS‐1377 G/A and FASL‐844 T/C polymorphisms were not associated with the risk of GCA. However, the FAS‐670 A/G genotype might decrease the risk of GCA for smoker individuals.     

Replication of results of genome‐wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population

Two recent genome‐wide association studies have identified that the rs2274223 single‐nucleotide polymorphism inphospholipase C epsilon 1 and the single‐nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high‐resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR] = 1.86, 95% confidence interval [CI] = 1.08–3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR = 0.71, 95% CI = 0.52–0.97) and no significant association in the older group (OR = 1.19, 95% CI = 0.87–1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case–control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.     

Genotypes of CYP1A1, SULT1A1 and SULT1A2 and risk of squamous cell carcinoma of esophagus: outcome of a case–control study from Kashmir,India

Studies on associations of various polymorphism in xenobiotic metabolizing genes with different cancers including esophageal squamous cell carcinoma (ESCC) are mixed and inconclusive. To evaluate the association of CYP1A1*4, SULT1A1*2 and SULT1A2*2 genotypes with ESCC risk and their modifying effects on different risk factors of ESCC, we conducted a case–control study in Kashmir, India, an area with relative high incidence of ESCC. We recruited 404 histopathologically confirmed ESCC cases, and equal number of controls, individually matched for sex, age and district of residence to respective case. Information was obtained on various dietary, lifestyle and environmental factors in face‐to‐face interviews, using a structured questionnaire, from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and direct sequencing. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A higher risk was observed in the subjects who harbored variant genotype of CYP1A1*4 (OR = 2.06; 95% CI: 1.28–3.32); and the risk was further enhanced in ever smokers (OR = 3.47; 95% CI: 1.62–7.42), adobe dwellers (OR = 6.71; 95% CI: 3.02–14.89), and biomass fuel users (OR = 5.11; 95% CI: 1.34–19.50). We did not find any significant differences in the polymorphic variants of SULT1A1*2 and SULT1A2*2 between cases and controls. The study indicates that, unlike SULT1A1*2 and SULT1A2*2, the polymorphism of CYP1A1*4 is associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate our findings.     

Association between positive murine double minute 2 expression and clinicopathological characteristics of esophageal squamous cell carcinoma: a meta‐analysis

The correlations of murine double minute 2 (MDM2) T309G and esophageal cancer were elucidated because the association between MDM2 expression states and clinicopathological parameters of esophageal squamous cell carcinoma (ESCC) is controversial. We conducted a meta‐analysis on studies screened from PubMed, Web of Science, Embase, the Cochrane Library, and the Chinese Biomedical Literature Databases that were published before October 2014. All studies describing the association between MDM2 and ESCC were traced. Meta‐analysis was performed using the STATA software (Stata Corp., College Station, TX, USA). A total of 9 studies with 707 cases and 324 controls were included. MDM2 expression was higher in ESCC than in normal esophageal epithelium (odds ratio [OR] 10.38, 95% confidence interval [CI] 6.42–16.78, P < 0.001). High MDM2 expression was associated with early primary tumor stage (T1/T2 vs. T3/T4, OR 0.59, 95% CI 0.38–0.92, P = 0.018) and increased risk of regional lymph node metastasis (N0 vs. N1, OR 1.66, 95% CI 1.03–2.67, P = 0.039). However, no relationship was observed between MDM2 expression and the risk of distant metastasis (OR = 2.09, 95% CI 1.00–4.36, P = 0.050), and MDM2 was not significantly correlated with TP53 expression (OR 1.22, 95% CI 0.53–2.77, P = 0.643). Our analysis suggests that MDM2 acts as a potent marker of early primary tumor stage but higher risk of regional lymph node metastasis in ESCC. However, because of the limited number of studies included, the result should be further clarified by well‐designed prospective studies.     

Human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma

There is currently no consensus on the relationship between human papillomavirus (HPV) infection and the pathogenic process of esophageal squamous cell carcinoma (ESCC). Therefore, a retrospective study was performed to explore the association between HPV infection and ESCC, where 225 patients with diagnosed ESCC and 224 matched controls were enrolled in the study and stratified according to smoking and alcohol consumption. Enzyme‐linked immunosorbent assay was used to determine seropositivity to HPV by the detection of either IgG or IgM anti‐HPV antibodies. In the non‐smoking and non‐alcohol‐consuming subgroup, the incidence of ESCC of HPV seropositive subjects was similar with that of HPV seronegative subjects (P= 0.737, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.54–2.40). However, in the smoking subgroup, there was a significant difference in the incidence of ESCC between HPV seropositive subjects and HPV seronegative subjects (P= 0.009, OR 2.22, 95% CI 1.22–4.04). In addition, there was a significantly higher association of the development of ESCC in HPV seropositive patients that smoke and drink than those that do not (P < 0.001, OR 10.31, 95% CI 4.04–26.29). Therefore, HPV infection is not an independent risk factor for developing ESCC in the non‐smoking and non‐alcohol‐consuming group. For smokers, however, HPV infection increases the risk of the incidence of ESCC.     

Association of genetic polymorphisms in PTEN and additional gene–gene interaction with risk of esophageal squamous cell carcinoma in Chinese Han population

This study aims to investigate the association of five single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homologue (PTEN) gene and additional role of gene–gene interaction with esophageal squamous cell carcinoma (ESCC), based on a Chinese case–control study. A total of 871 subjects (420 males and 451 females) were selected, including 425 ESCC cases and 446 controls. Five SNPs were selected for genotyping in the case–control study: rs2735343, rs555895, rs2299939, rs17431184 and rs701848. Logistic regression model was used to examine the association between five SNP and ESCC, and additional interaction among five SNP, odds ratio (OR) and 95% confident interval (95%CI) were calculated. All genotypes were distributed according to Hardy–Weinberg equilibrium in controls. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk than those with wild‐type homozygotes, and OR (95%CI) were 1.27 (1.09–2.08) and 1.45 (1.17–1.98), respectively. We also found a potential gene–gene interaction between rs2735343 and rs701848 (P = 0.0010), and a potential gene–gene interaction among all five SNP (P = 0.0107) after covariates adjustment. Subjects with TC or CC of rs2735343 and TC or CC of rs701848 genotype have highest ESCC risk, compared to subjects with TT of rs2735343 and TT of rs701848 genotype, OR (95% CI) was 2.76 (1.37–3.45) after covariates adjustment. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk. We also found a potential gene–gene interaction between rs2735343 and rs701848 and a potential gene–gene interaction among all five SNPs.     

Polymorphisms of the DNA repair gene xeroderma pigmentosum groups A and C and risk of esophageal squamous cell carcinoma in a population of high incidence region of North China

Aim Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity (DRC) and genetic susceptibility to different cancers. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum group A (XPA) and XPC can influence the risk of esophageal squamous cell carcinoma (ESCC). Methods In this report, one SNP of XPA and three SNPs of XPC were genotyped by polymerase-chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP) assay in 327 ESCC patients and 612 healthy controls in a high incidence region of North China. Results Family history of upper gastrointestinal cancers (UGIC) may increase the risk of developing ESCC. The overall genotype and allelotype distributions of XPA A23G in ESCC patients were significantly different from that in healthy controls (P < 0.05). The A/G + G/G genotype significantly decreased the risk of developing ESCC compared with A/A genotype. When stratified for family history of UGIC, compared with A/A genotype, A/G + G/G genotype significantly decreased the risk of ESCC in groups with negative history of UGIC. The overall genotype and allelotype distributions of XPC intron 9 PAT^+/- and exon 15 Lys939Gln and exon 8 Val499Ala in ESCC patients were not significantly different from that in healthy controls (P > 0.05). When stratified for smoking status and UGIC family history, compared with A/A genotype, C/C genotype of exon 15 Lys939Gln significantly increased the risk of developing ESCC in non-smoker group. Conclusions We concluded that XPA23 polymorphism may be useful markers for identifying individuals at risk of developing ESCC. C/C genotype of XPC exon 15 may be one of the factors that affect the risk of developing ESCC in nonsmoking population in the high incidence region of China.     

p53 codon 72 polymorphism and the risk of esophageal cancer: a Korean case‐control study

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case‐control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real‐time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85–1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02–2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92–1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15–2.74) for EC overall. In never‐smokers and ever‐smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37–0.95) and 1.39 (95% CI = 1.00–1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case‐control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.     

P53 gene codon 72 polymorphism and risk of esophageal squamous cell carcinoma: a case/control study in a Chinese population

SUMMARY.  The aims of this study were to investigate whether p53 gene codon 72 polymorphism was a biomarker associated with esophageal squamous cell carcinoma (ESCC) and its relationship with smoking status in China. The p53 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism among 673 patients with ESCC and 694 healthy controls. The association between p53 genotypes and risk of developing ESCC was estimated by odds ratios (OR) and their 95% confidence intervals (CIs) computed by logistic regression. Compared with Arg/Arg homozygotes, Pro/Pro homozygotes had a nearly twofold increased risk (adjusted OR, 1.83; 95% CI, 1.35–2.48). For the Pro/Arg heterozygotes, there was no evident increased risk (adjusted OR, 1.01, 95% CI, 0.78–1.30). Furthermore, the risk associated with the Pro/Pro variant genotype was more pronounced in younger patients at diagnosis (= 45 years) (OR, 7.4; 95% CI, 1.44–37.89, P  = 0.02), in women (OR, 3.15; 95% CI, 1.52–4.53, P  = 0.02) and in non-smokers (OR, 2.49; 95% CI, 1.58–3.94) and light smokers (OR, 2.13; 95% CI, 1.15–3.93). But tests for homogeneity between smoking-related OR showed no significant differences ( P  = 0.4). The p53 gene codon 72 Pro/Pro genotype was significantly associated with the increased risk of ESCC in a Chinese mainland population and may be an independent factor in susceptibility to ESCC. The association was especially noteworthy in women and in younger patients.     

Association of Helicobacter pylori infection with esophageal adenocarcinoma and squamous cell carcinoma: a meta‐analysis

To evaluate the relationship of Helicobacter pylori and cytotoxin‐associated gene A (CagA) positive strains with esophageal neoplasm, including esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), the authors conducted a meta‐analysis using a predefined protocol. PubMed, Web of Science, China biology medical literature database, Wanfang, and China National Knowledge Infrastructure were searched for relevant articles from the first available year to April 8, 2013. The fixed or random effect pooled measure was selected based on heterogeneity among studies, which was evaluated using Q test and the I² of Higgins and Thompson. Metaregression was used to explore the sources of between‐study heterogeneity. Publication bias was analyzed by Begg's funnel plot and Egger's regression test. The association was assessed by odds ratio (OR) with 95% confidence interval (CI). A total of 28 eligible studies were included in the meta‐analysis. There was a significant inverse association between H. pylori infection (pooled OR, 0.57; 95% CI, 0.44–0.73) and EAC; CagA‐positive H. pylori strains were less likely to be associated with EAC compared with CagA‐negative strains (pooled OR, 0.64; 95% CI, 0.52–0.79). However, there was no statistically significant association between H. pylori/CagA‐positive H. pylori strains infection and ESCC, and the pooled ORs were 1.16 (95% CI, 0.83–1.60) and 0.97 (95% CI, 0.79–1.19). But significant associations between CagA‐positive H. pylori strains infection and ESCC risk were found in the stratified analysis of the study location (Asian and non‐Asian), and the summary ORs were 0.74 (95% CI, 0.57–0.97) and 1.41 (95% CI, 1.02–1.94). H. pylori infection and CagA‐positive strains are associated with decreased risk of EAC in the overall population. No significant association was found between H. pylori infection/CagA‐positive strains and ESCC. But CagA‐positive strains might have a positive association with ESCC in non‐Asian population and an inverse association in Asian population.     

No association of the matrix metalloproteinase 1 promoter polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in northern China

AIM: To investigate association of the 2Gor1Gsingle nudeotide polymorphism (SNP) in matrix metalloproteinase 1 (MMP1) promoter with susceptibility to esophageal squam-ous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of North China. METHODS: MMP1 promoter SNP was genotyped by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 417 cancer patients (234 ESCC and 183 GCA) and 350 healthy controls. RESULTS: The genotype frequencies of the MMP1 promoter SNP in healthy controls were 55.4% (2G/2G), 30% (1G/2G) and 14.6% (1G/1G), respectively. The genotype and allelotype distribution in ESCC and GCA patients was not significantly different from that in healthy controls (all lvalues were above 0.05). Compared with the 1G/1Ggenotype, neither the 2G/2Gnor in combination with the 1G/2G genotype significantly modified the risk of developing ESCC and GCA, the adjusted odds ratio was 1.28 (95%CI = 0.78-2.09), 1.23 (95%CI = 0.38-2.05) in ESCC and 1.39 (95%CI = 0.80-2.41), 1.34 (95%CI = 0.74-2.40) in GCA, respectively. When stratified by smoking status and family history of upper gastrointestinal cancer, the 2G/2Ggenotype alone or in combination with the 1G/2G genotype also did not show any significant influence on the risk of ESCC and GCA development. In addition, influence of the MMP1 SNP on lymphatic metastasis in ESCC and GCA was also not obs-erved. CONCLUSION: The 2Gor 1GSNP in the MMP1 promoter might not modify the risk of ESCC and GCA development and might not be used as a stratification marker to predict the potential of lymphatic metastasis in these two tumor types.     

Meta‐analysis of alcohol consumption and risk of extrahepatic bile system cancer

Aim: Alcohol consumption increases the risk of liver cancer. However, there is still controversy regarding alcohol consumption and the risk of extrahepatic bile system cancer (EBSC). We performed a meta‐analysis to provide an overview of the relevant studies and gain more robust estimates of the relationship between alcohol consumption and risk of EBSC. Methods: Relevant studies published between January 1966 and October 2010 were identified by searching Medline, Embase and the Cochrane Library. Studies were selected using a priori defined criteria. The strength of the relationship between alcohol consumption and risk of EBSC was assessed by adjusted odds ratio (OR). Results: A total of 113 767 participants from 10 studies (nine case–control studies and one cohort study) were identified in this meta‐analysis. The studies provided adjusted overall OR estimates for drinkers versus non‐/low drinkers, leading to a pooled adjusted OR of 0.82 (95% confidence interval [CI] = 0.72–0.94, P for heterogeneity = 0.194, I² = 27.2%). The overall adjusted OR of hospital‐based studies and population‐based studies were 0.80 (95% CI = 0.65–0.99, P = 0.260) and 0.79 (95% CI = 0.64–0.98, P = 0.119), respectively. For the heavy drinkers, the adjusted OR significance increased to 1.58 (95% CI = 0.97–2.57, P for heterogeneity = 0.055, I² = 65.4%), but it had no statistical significance. Conclusion: There is evidence that moderate alcohol consumption lowers the risk of EBSC compared with non‐/low alcohol consumption, but not heavy alcohol consumption. Further multicenter and better controlled studies are required to confirm these findings.     

Significant association between asthma risk and the GSTM1 and GSTT1 deletion polymorphisms: An updated meta‐analysis of case–control studies

Polymorphisms in GSTM1 and GSTT1 may be associated with asthma risk, yet several studies and meta‐analyses have reported inconclusive results. Therefore, an updated meta‐analysis was conducted. Literature searches were performed using the Pubmed, Embase and Web of Science databases until October 2012. Variant ‘null’ genotype was compared with wild‐type ‘present’ in the pooled data. All statistical analyses were performed using STATA 11.0. A total of 26 case–control studies were suitable for inclusion in the meta‐analysis. In the overall population, a significant association was found for both the GSTM1 (odds ratio (OR) = 1.452; 95% confidence interval (CI): 1.192–1.770) and GSTT1 polymorphism (OR = 1.792; 95% CI:1.293–2.483). For subgroup analysis by age, GSTM1 significantly increased risk for both children (OR = 1.368; 95% CI: 1.051–1.781) and adults (OR = 1.859; 95% CI: 1.183–2.921). For GSTT1, a significant association was only found in the adult population (OR = 2.312; 95%CI: 1.204–4.439). Based on subgroup analysis by ethnicity, a significant association for GSTM1 was found in Europe (OR = 1.303; 95% CI: 1.018–1.667), Africa (OR = 2.175; 95%CI: 1.560–3.031) and Latin America (OR = 2.265; 95%CI: 1.375–3.729). For GSTT1, significantly increased risk was found only for Asian (OR = 2.105; 95% CI: 1.101–4.025) and Russian (OR = 2.747; 95% CI: 1.071–7.046) populations. This meta‐analysis provides evidence that GSTM1 and GSTT1 polymorphisms may be risk factors for asthma.     

PTEN hypermethylation profiles of Chinese Kazakh patients with esophageal squamous cell carcinoma

Aberrant DNA methylation of promoter region CpG islands may serve as an alternative mechanism to genetic defects in the inactivation of tumor suppressor genes (TSGs) in human malignancies. The aim of this study was to examine the promoter methylation status of the PTEN TSG and its association with esophageal squamous cell carcinoma (ESCC) carcinogenesis in a Chinese Kazakh population, which is known to have a relatively high ESCC incidence and mortality. The methylation status of the PTEN promoter region was determined in patients with ESCC (n = 95) and healthy individuals (n = 65) using highly sensitive Sequenom Epityper assays. The methylation level of the PTEN gene was significantly higher in patients with ESCC than in healthy controls. The median methylation level was 10.0% (interquartile range [IQR]: 7.0–11.0%) in patients with ESCC and 6.0% in controls (IQR: 4.0–9.0%; P = 0.001). PTEN methylation levels were higher in male patients with ESCC than in male controls, whereas a trend toward significance was observed between female patients with ESCC and female controls (P = 0.005 and P = 0.086, respectively). The PTEN methylation level was associated with histopathological grade and lymph node metastasis in patients with ESCC (P = 0.002 and P = 0.009, respectively). To our knowledge, this is the first report to show the presence of PTEN promoter CpG hypermethylation in ESCC and its association with tumor metastasis.